Sex hormones have profound influences on many aspects of health and disease. The beneficial effects of hormone replacement therapy (HRT) on cardiovascular health, osteoporosis, and cognitive function of postmenopausal women have been well-documented. However, a scant amount of data is available on the effects of HRT on immune function. Prior to menopause, females have markedly more vigorous humoral and cellular immune responses than males. Examples of this more robust immunity include higher antibody responses to various microorganisms after immunization, more efficient rejection of allografts, relative resistance to immunotolerance, and increased survival during bacterial sepsis. On the other hand, pre-menopausal females also show markedly increased incidence of autoimmune diseases, such as SLE, autoimmune thyroiditis, and MS. Given the potent effect of endogenous estrogen on immune function, we hypothesize that HRT will similarly exert a strong influence on immune function. However, the effects may not precisely mirror estrogen effects during early life since aging itself has a dramatic impact on immune function. The goal of this Pilot Project is, therefore, to perform a series of Preliminary Studies to compare immune system of two cohorts of postmenopausal women: one untreated and one being treated with HRT. The following assays will be performed to evalulate immune function: (1) Flow cytometric enumeration of cellular composition of peripheral blood (2) Functional testing of T cell proliferative response and apoptosis; (3) evaluation of constitutive cytokine levels in serum (4) Assessment of circulating levels of autoantibodies. This research will provide new information of a variety of immune parameters which we and others have previously documented to change with age but which have never been investigated in the context of HRT. Postmenopausal women constitute an increasingly large proportion of the population. A precise evaluation of the effects of hormone replacement therapy will provide critical information on their health status, and furthermore, will also add much needed data on the overall benefits and risks of this common medical intervention. This study will also advance the NIH strategic plan which emphasizes research on women's health.